This invention relates to devices and methods for delivering an aerosolized liquid to a user""s lungs, and particularly an aerosolized liquid having therapeutic properties.
For some therapeutic agents, delivery of the aerosolized liquid without a propellant is preferred. Such liquids may be aerosolized, for example, by an electrohydrodynamic apparatus. The liquid to be aerosolized is made to flow over a region of high electric field strength, which imparts a net electric charge to the liquid. This electric charge tends to remain on the surface of the liquid such that, as the liquid exits the nozzle, the repelling force of the surface charge balances against the surface tension of the liquid, forming a cone (a xe2x80x9cTaylor conexe2x80x9d as described in, e.g., M. Cloupeau and B. Prunet-Foch, xe2x80x9cElectrohydrodynamic Spraying Functioning Modes: A Critical Review,xe2x80x9d J Aerosol Sci., Vol. 25, No. 6, pp. 1021, 1025-1026 (1994)). In the region of the tip of the cone, which has the greatest charge concentration, the electrical force exerted on the liquid surface overcomes the surface tension, generating a thin jet of liquid. The jet breaks into droplets of more or less uniform size, which collectively form a cloud that may be inhaled by a user to deliver the aerosol to the user""s lungs.
Dr. Ronald Coffee of Oxford University, Oxford, England, has proposed and developed methods of aerosolizing pharmaceutical formulations and discharging the aerosol particles prior to their delivery to a user. One such method uses an electrohydrodynamic apparatus having a single spray site (nozzle) surrounded by four discharge electrodes and a grounded shield to produce a monodispersed spectrum of particle sizes.
Known pulmonary delivery devices that use electrohydrodynamic spraying are unwieldy and require connection to either an alternating current power supply or a large direct current power supply. These conventional devices are suitable for use in hospital or other clinical applications, such as for administering a therapeutic agent during a scheduled treatment appointment, but generally are not suitable for use directly by a user on a demand or as-needed basis outside a clinical setting. Conventional devices are particularly unsuited for use during a user""s regular activities at home, at work, while traveling, and during recreational and leisure activities.
Known pulmonary delivery devices that use electrohydrodynamic spraying also lack a sufficient volumetric flow rate to deliver a desired amount of certain therapeutic liquids during the inhalation of one to two breaths by a user. Attempts to increase the flow rate generally have resulted in even more bulky devices unsuitable for hand-held use. These delivery devices also are not generally capable of spraying liquids having a broad range of conductivities.
It is an object of the invention to provide a device and method that conveniently delivers an aerosolized liquid to a user""s lungs. It is another object of the invention to provide a compact, portable, hand-held pulmonary delivery device that may be used in a variety of indoor and outdoor locations. The device would allow users to administer therapeutic agents on an as-needed basis in nonclinical settings and provide advantages over conventional devices used by hospitals and clinicians.
It is a further object of the invention to provide a compact and convenient device and method that delivers an increased volumetric flow rate of liquid so that a desired amount of a therapeutic liquid dispersed into respirable particles may be administered during the inhalation of one to two breaths by a user.
It is another object of the invention to provide a device and method capable of electrohydrodynamic spraying of therapeutic liquids having a broad conductivity range in a compact and convenient device.
It is yet another object of the invention to provide an apparatus for aerosolizing liquid that is useful in the delivery to a user, in the form of respirable particles, of a desired amount of a therapeutic liquid within a broad conductivity range.
The invention described here provides a compact, convenient device and method for delivering an aerosolized liquid having therapeutic properties to a user""s lungs by electrohydrodynamic spraying. Preferably, the device is small enough that it can be comfortably carried by a user, for example, in shirt pocket or purse, and has a self-contained power supply so that it can be used anywhere. The device may be disposable. or reusable.
In a preferred embodiment, the pulmonary aerosol delivery device comprises a housing sized so that it can be held in a user""s hand and having an exit opening for directing the aerosol to the user""s mouth. The housing encloses a dispensing system for containing the liquid to be aerosolized and delivering it to an electrohydrodynamic apparatus, an electrohydrodynamic apparatus for aerosolizing the liquid and delivering the aerosol to the exit opening; and a power supply system for providing sufficient voltage to the electrohydrodynamic apparatus to aerosolize the liquid. The power supply system may comprise a battery and a DC to DC high voltage converter so the device may be cordless.
The liquid to be aerosolized may comprise a drug. The dispensing system of the device may include a containment vessel for containing the drug, which may be a holder for a drug enclosed in single dose units, a plurality of sealed chambers each holding a single dose of a drug, or a vial for enclosing a bulk supply of a drug. The containment vessel may have antimicrobial properties and may be capable of maintaining the sterility of a sterile drug placed therein.
The dispensing system delivers a single dose of the drug from the containment vessel to the electrohydrodynamic apparatus, which may be accomplished using a metering system. The metering system may include a chamber for collecting a predetermined volume of liquid having an inlet communicating with the containment vessel and an outlet communicating with the electrohydrodynamic apparatus; a chamber housing above the chamber; a chamber housing spring adjacent to the chamber; and a button spring above the chamber housing. The button spring exerts a downward force against the chamber housing when an actuator button is depressed to force liquid in the chamber through the outlet and the chamber housing spring exerts an upward force against the chamber housing when the actuator button is released. The upward travel of the chamber housing induces a vacuum in the chamber to draw liquid from the containment vessel through the inlet. The chamber volume is controlled by an adjustable stop that limits the upward travel of the chamber housing. The metering system may further include check valves at the chamber inlet and outlet to provide unidirectional liquid flow.
The device may further include a control circuit communicating with the dispensing system, the electrohydrodynamic apparatus and the power supply system. The control circuit may include an on/off power indicator, a power save feature, or a lockout to prevent use by an unauthorized user.
The control circuit may include an actuation device for initiating the flow of aerosolized liquid. The actuation device may be a breath sensor for detecting a user""s inhalation of one or more breaths, such as a flapper switch, a pressure transducer, an air motion detector, or an air velocity detector, which cooperates with the electrohydrodynamic apparatus to initiate the flow of aerosolized liquid. The actuation device also may be a manual actuator on the exterior of the housing.
The electrohydrodynamic apparatus of the device may be capable of aerosolizing the liquid at a flow rate of at least about 20 xcexcL/sec. It also may be capable of aerosolizing the liquid into droplets such that at least about 80% of the droplets have a diameter of less than or equal to about 5 microns.
The housing of the device may have antimicrobial properties. The exit opening of the housing may be movable to assist in directing the aerosol to the user""s mouth.
In another preferred embodiment, a pulmonary aerosol delivery device includes a housing sized so it can be held in a user""s hand and having an exit opening for directing the aerosol to the user""s mouth. The housing encloses a containment vessel holding a liquid to be aerosolized, an electrohydrodynamic apparatus for aerosolizing the liquid and delivering the aerosol to the exit opening, a power supply for providing sufficient voltage to the electrohydrodynamic apparatus to aerosolize the liquid, and a dispensing system for delivering the liquid to be aerosolized from the containment vessel to the electrohydrodynamic system.
The dispensing system may include a metering system for dispensing a desired amount of the liquid to the electrohydrodynamic apparatus, which may comprise a mechanically-actuated piston pump. The metering system and the control circuit may cooperate to provide a dose counter or a dose display, which may show the doses administered or the doses remaining. The control circuit may include a timer that cooperates to limit the delivery of the liquid by the metering system. The control circuit also may include a signal that cooperates with the timer to alert a user that a dose is due by an alarm or a visual display showing the time when the next dose is due. The control circuit includes a memory for storing dose information to be provided to the metering system or recording the dose history.
The electrohydrodynamic apparatus of the device may include a charge neutralizer for aiding in the delivery of the drug to a user""s lungs. The electrohydrodynamic apparatus also may include a generally circular base plate having upper and lower surfaces; a plurality of spray sites arranged in a circular pattern along the perimeter of the lower surface of the base plate, each of the spray sites having a base end mounted to the base plate and a tip end oriented vertically downward; a skirt extending downward from the base plate; a plurality of discharge electrodes each extending radially inward from the skirt in the area of the spray site tip ends; and a plurality of reference electrodes each extending radially inward from the skirt downstream of and between the discharge electrodes. A dielectric material may be enclosed within the skirt or the skirt may be comprised of a dielectric material.
The tip end of at least one spray site may be chamfered. The exterior of at least one of the spray sites also may be coated with a low surface energy coating. The electrohydrodynamic apparatus further may include a manifold extending between the dispensing system and the base ends of the spray sites.
In another preferred embodiment, the pulmonary aerosol delivery device includes a housing sized so it can be held in a user""s hand and having an exit opening for directing the aerosol to the user""s mouth. The housing includes a dispensing system for containing the liquid to be aerosolized and delivering it to an electrohydrodynamic apparatus; an electrohydrodynamic apparatus for aerosolizing the liquid and delivering the aerosol to the exit opening; and a power supply system for providing sufficient voltage to the electrohydrodynamic apparatus to aerosolize the liquid. The electrohydrodynamic device includes a spray site having a sufficient electric field strength that a net electrical charge is imparted to the surface of a liquid flowing over the spray site, with the surface charge initially balancing the surface tension of the liquid to cause the liquid to form a cone and eventually overcoming the surface tension of the liquid in the region of the tip of the cone to generate a thin jet of liquid that breaks into droplets of respirable size.
In a preferred embodiment, the method of orally administering an aerosolized liquid therapeutic agent includes the steps of:
storing the liquid in a containment vessel;
dispensing the liquid from the containment vessel to an electrohydrodynamic apparatus;
electrically actuating the electrohydrodynamic apparatus to aerosolize the liquid;
metering a desired amount of liquid to be dispensed from the containment vessel to the electrohydrodynamic apparatus; and
enclosing the containment vessel and electrohydrodynamic apparatus within a cordless housing of such size that it can be held in a user""s one hand, the housing including an exit opening for directing the aerosol to the user""s mouth.
In the above-described method, the treating step may include neutralizing the electrical charge imparted to the aerosolized liquid and the electrical actuation step may be initiated by a user""s inhalation of breath.
In another preferred embodiment, the method for orally administering an aerosolized liquid therapeutic agent comprises the steps of:
storing the liquid in a containment vessel;
metering a desired amount of liquid to be dispensed from the containment vessel to the electrohydrodynamic apparatus;
dispensing the liquid from the containment vessel to an electrohydrodynamic apparatus;
electrically actuating the electrohydrodynamic apparatus to aerosolize the liquid;
treating the aerosolized liquid to modify an electrical charge imparted to the aerosolized liquid by the electrohydrodynamic apparatus; and
enclosing the containment vessel and electrohydrodynamic apparatus within a cordless housing of such size that it can be held in a user""s one hand, the housing including an exit opening for directing the aerosol to the user""s mouth.
The electrical actuation step may be initiated by a user""s inhalation of breath.
Another preferred embodiment of the pulmonary aerosol delivery device comprises a housing of such size that it can be held in a user""s one hand, the housing having an exit opening for directing the aerosol to the user""s mouth and including therein, a dispensing system for containing the liquid to be aerosolized and delivering it to an apparatus for aerosolizing the liquid; an apparatus for aerosolizing the liquid and delivering the aerosol to the exit opening; and a power supply system for providing sufficient voltage to the aerosolizing apparatus to aerosolize the liquid. The apparatus for aerosolizing the liquid comprises a plurality of spray sites each having a tip end, the spray sites cooperating with a charge source to result in an electrohydrodynamic spray from at least one tip end, a plurality of discharge electrodes downstream of the tip ends, and a plurality of reference electrodes downstream of the plurality of discharge electrodes.
The invention also encompasses an apparatus for aerosolizing a liquid. In one preferred embodiment, the aerosolizing apparatus comprises a plurality of spray sites each having a tip end, the spray sites cooperating with a charge source to result in an aerosolized spray from at least one tip end, a plurality of discharge electrodes downstream of the tip ends, and a plurality of reference electrodes downstream of the plurality of discharge electrodes. The apparatus also may include a charge source for charging the spray sites sufficiently to result in an electrohydrodynamic spray from at least one tip end.
The plurality of discharge electrodes and the plurality of reference electrodes may be oriented toward the aerosolized spray and particularly may be oriented radially toward the aerosolized spray. Preferably, the plurality of discharge electrodes are spaced equidistant from one another and the plurality of reference electrodes are located in the interstices between the discharge electrodes.
The aerosolizing apparatus also may include a dielectric material between the plurality of discharge electrodes and the plurality of reference electrodes. The reference electrodes may extend through slots provided in the dielectric material.
Preferably, at least one of the plurality of spray sites has a sufficient electric field strength that a net electrical charge is imparted to the surface of a liquid flowing over the spray site such that the surface charge initially balances the surface tension of the liquid to cause the liquid to form a cone and eventually overcomes the surface tension of the liquid in the region of the tip of the cone to generate a thin jet of liquid that breaks into aerosolized droplets of respirable size. At least one of the plurality of discharge electrodes may have a sufficient electric field strength to substantially neutralize a charge on the aerosolized droplets generated by the spray site.
The tip ends of the plurality of spray sites may be oriented vertically downward. Preferably, the plurality of spray sites are arranged in a generally circular pattern and are spaced equidistant from one another. The tip end of at least one of the plurality of spray sites may be chamfered. Also, the exterior of at least one of the plurality of spray sites may be coated with a low surface energy coating.
Another preferred aerosolizing apparatus comprises a tubular base having a generally circular cross-section, a plurality of spray sites each having a tip end extending axially into a first end of the base, the spray sites cooperating with a charge source to result in an aerosolized spray from at least one tip end, a plurality of discharge electrodes each connected to the interior of the base downstream of the spray sites, and a plurality of reference electrodes each connected to the interior of the base downstream of the plurality of discharge electrodes. The apparatus may further include a charge source for charging the spray sites sufficiently to result in an electrohydrodynamic spray from at least one tip end.
Preferably, the plurality of discharge electrodes and the plurality of reference electrodes are oriented toward the aerosolized spray. The plurality of discharge electrodes may be located in the area of the tip ends of the plurality of spray sites.
In the above-described aerosolizing apparatus, at least one of the plurality of spray sites preferably has a sufficient electric field strength that a net electrical charge is imparted to the surface of a liquid flowing over the spray site such that the surface charge initially balances the surface tension of the liquid to cause the liquid to form a cone and eventually overcomes the surface tension of the liquid in the region of the tip of the cone to generate a thin jet of liquid that breaks into aerosolized droplets of respirable size. At least one of the plurality of discharge electrodes may have a sufficient electric field strength to substantially neutralize a charge on the aerosolized droplets generated by the spray site.
The plurality of reference electrodes and the plurality of discharge electrodes may extend radially inwardly from the interior of the base. The plurality of discharge electrodes preferably are spaced equidistant from one another and the plurality of reference electrodes are located in the interstices between the discharge electrodes.
The aerosolizing apparatus also may include a dielectric material within the base between the discharge electrodes and the reference electrodes. Preferably, the reference electrodes extend through slots provided in the dielectric material.
The tip ends of the plurality of spray sites provided in the aerosolizing apparatus preferably are oriented vertically downward. The plurality of spray sites may be arranged in a predetermined pattern, and particularly in a generally circular pattern.
In yet another preferred embodiment, the aerosolizing apparatus comprises a generally circular base plate having upper and lower surfaces, a plurality of spray sites arranged in a circular pattern along the perimeter of the lower surface of the base plate, each of the spray sites having a base end mounted to the base plate and a tip end, the spray sites cooperating with a charge source to result in an aerosolized spray from at least one tip end, a skirt extending downward from the base plate, a plurality of discharge electrodes each extending from the skirt downstream of the spray site tip ends; a plurality of reference electrodes each extending from the skirt downstream of the discharge electrodes, and a dielectric material between the plurality of discharge electrodes and the plurality of reference electrodes. The dielectric material may be a discrete member provided within the skirt or the skirt may be comprised of a dielectric material. The aerosolizing apparatus also may include a charge source for charging the spray sites sufficiently to result in an electrohydrodynamic spray from at least one tip end.
The plurality of reference electrodes may be positioned in interstices between the discharge electrodes. Preferably, the plurality of discharge electrodes are spaced equidistant from one another with the plurality of reference electrodes are located in the interstices between the discharge electrodes. The reference electrodes may extend through slots provided in the dielectric material.
In the above-described aerosolizing apparatus, at least one of the plurality of spray sites preferably has a sufficient electric field strength that a net electrical charge is imparted to the surface of a liquid flowing over the spray site such that the surface charge initially balances the surface tension of the liquid to cause the liquid to form a cone and eventually overcomes the surface tension of the liquid in the region of the tip of the cone to generate a thin jet of liquid that breaks into droplets of respirable size. At least one of the plurality of discharge electrodes may have a sufficient electric field strength to substantially neutralize a charge on the aerosolized droplets generated by the spray site.
These and further objects of the invention will become apparent from the following detailed description.